P785: SIX-MONTH CROVALIMAB EXTENSION IN THE PHASE 3 COMMODORE 3 STUDY: UPDATED EFFICACY AND SAFETY RESULTS IN COMPLEMENT INHIBITOR-NAIVE PATIENTS (PTS) WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
Authors: Hui Liu, Linghui Xia, Jianyu Weng, Fengkui Zhang, Chuan He, Sujun Gao, Jinsong Jia, Alice Chang, Wenjin LI, Sasha Sreckovic, Dayu Shi, Zilu Zhang, Rong Fu
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: The primary analysis of the Phase 3 multicenter single-arm COMMODORE 3 (NCT04654468) trial studying crovalimab (a novel C5 inhibitor) in C5 inhibitor-naive pts with PNH in China reported that both co-primary endpoints of hemolysis control and transfusion avoidance were met, with no new safety signals (Liu ASH 2022). Aims: Report updated COMMODORE 3 data with an additional 6 months of crovalimab exposure. Methods: The study enrolled Chinese pts with PNH who were ≥12 years, ≥40 kg, had lactate dehydrogenase (LDH) ≥2×upper limit of normal (ULN) and ≥4 transfusions of packed red blood cells (pRBCs) 1 year before screening. Pts were ineligible if they received prior C5 inhibitor treatment. Pts received crovalimab per a weight-based dosing schedule, including loading (1× intravenous dose on Day 1, followed by 4× weekly subcutaneous (SC) doses starting from Day 2) and SC maintenance doses (every 4 weeks [q4w] starting from Week[W] 5); treatment continued after 24 wks in pts with clinical benefit. Updated exploratory efficacy analyses were conducted in the interval analysis population (IAP) defined as pts who had ≥1 LDH assessment and ≥1 crovalimab dose from W25 to W49. Exploratory efficacy endpoints were: proportion of pts achieving hemolysis control (LDH ≤1.5×ULN), proportion of pts achieving transfusion avoidance, proportion of pts with breakthrough hemolysis (BTH), proportion of pts with hemoglobin stabilization, and change in fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scale). Safety and immunogenicity were also assessed. All results are descriptive. Results: Baseline characteristics of enrolled pts (N=51) have been reported (Liu ASH 2022). IAP included 50 pts. At clinical cutoff (Aug 10, 2022), pts maintained disease control throughout the crovalimab extension period from W25 to W49 (Table). Proportion of pts achieving hemolysis control was 77.8% (95% CI: 57.7, 91.4) at W49. Proportion of pts with transfusion avoidance from W25 to W49 was 60.0% (95% CI: 45.2, 73.3). Mean number of pRBC units transfused per patient from W25 to W49 was 4.1 (SD, 6.7). BTH was seen in 2 pts (4.0%; 95% CI: 0.7, 14.9) from W25 to W49. Proportion of pts with hemoglobin stabilization from W25 to W49 was 56.0% (95% CI: 41.3, 69.7). Clinically meaningful improvement in mean FACIT-Fatigue score (≥5 points) during the primary analysis from baseline to W17 was sustained through W49. The safety population included 51 pts. Most AEs were lab abnormalities already present at baseline; worsening of these lab abnormalities was not associated with clinical consequences. From W25 to W49, 2 pts (4.0%) had new serious AEs (Grade 2 melanocytic naevus and Grade 3 breast disorder; n=1 each, not treatment related). Two pts (5.9%) had new Grade 3 AEs (urinary tract infection [treatment related] and dental caries [not treatment related]; n=1 each). No new deaths, Grade 4 AEs, AEs leading to withdrawal of treatment or dose modification or interruption, or serious treatment-related AEs were reported from W25 to W49. No pt had meningococcal infection. Treatment-emergent anti-drug antibodies (ADA) were detected in 18 of 51 pts (35.3%), of whom 2 (4%) were detected from W25 to W49. No pt developed neutralizing antibodies. There was no evidence for different efficacy and safety by ADA status and in 3 pts 12–18 years. Summary/Conclusion: In this updated analysis of COMMODORE 3, key efficacy results throughout the 6-month crovalimab extension period were consistent with the primary analysis, with no new safety signals, further confirming that crovalimab is efficacious and well tolerated in pts with PNH.Keywords: Clinical outcome, Clinical trial, Clinical data, Paroxysmal nocturnal hemoglobinuria (PNH)